The objective of this proposal is to determine the role of prostaglandins and cyclic nucleotides in immunological and inflammatory reactions, and investigate means whereby these compounds might modulate inflammation and tissue injury. The responses (prostaglandin and cyclic nucleotide production, enzyme release) of synovial cells in tissue culture to challenge by immune complexes and soluble and particulate antigens will be studied. Biochemical studies will be correlated with synovial cell ultrastructure. Lymphocytes from patients with multiple sclerosis (MS) adhere in significantly greater numbers to virus infected human epithelial (Hep-2) cells than lymphocytes from healthy controls, and adhere less avidly than control lymphocytes to sheep red blood cells. These altered in vitro cell-cell interactions in MS patients appear due to a common defect in a prostaglandin sensitive regulatory mechanism. We will study prostaglandin metabolism in MS leukocytes, and mechanisms responsible for the altered cell-cell interactions. Prostaglandin E1 (PGE1) treatment of NZB/W mice prevent nephritis and increases survival of these animal models of human systemic lupus erythematosus. We will study the effect of PGE1 and other prostaglandin analogues on immune responses in NZB/W mice. Chediak-Higashi (CH) syndrome is a genetic disorder of children and certain animal species including the beige mouse. Children with the disorder often succumb to infection because their polymorphonuclear leukocytes (PMN) exhibit impaired degranulation and bactericidal activity. We will study means whereby degranulation in CH PMN may be accelerated.